The effect of substance P on the cardiodynamics of an isolated, working rat heart preparation was examined. The peptide was found to have no influence on aortic pressure, cardiac output, or cardic work. However, a 10-15% reduction in coronary flow was observed over the concentration range of 10 to the minus eight to 10 to the minus six M. The octapeptide analogue of substance P also exhibited a similar vasoconstrictive effect, but at a much lower concentration; its ED(50) of 2 x 10 to the minus thirteen M was several orders of magnitude less than the ED(50) of substance P (ED(50) = 3.5 x 10 to the minus four M) eliminated the vasoconstrictive effect of substance P but not that of the octapeptide substance P. Thus, we conclude that a breakdown product (e.g. the octa-peptide) of Substance P is responsible for the observed decrease in coronary flow.